DOI: 10.1101/513135Jan 9, 2019Paper

Phosphorylation of mitochondrial matrix proteins regulates their selective mitophagic degradation

BioRxiv : the Preprint Server for Biology
Panagiota KolitsidaHagai Abeliovich


Mitophagy is an important quality control mechanism in eukaryotic cells, and defects in mitophagy correlate with aging phenomena and neurodegenerative disorders. It is known that different mitochondrial matrix proteins undergo mitophagy with very different rates, but to date the mechanism underlying this selectivity at the individual protein level has remained obscure. We now present evidence indicating that protein phosphorylation within the mitochondrial matrix plays a mechanistic role in regulating selective mitophagic degradation in yeast, via involvement of the Aup1 mitochondrial protein phosphatase, as well as two known matrix-localized protein kinases, Pkp1 and Pkp2. By focusing on a specific matrix phosphoprotein reporter, we also demonstrate that phospho-mimetic and non-phosphorylatable point mutations at known phosphosites in the reporter increased or decreased its tendency to undergo mitophagy. Finally, we show that phosphorylation of the reporter protein is dynamically regulated during mitophagy, in an Aup1-dependent manner. Our results indicate that structural determinants on a mitochondrial matrix protein can govern its mitophagic fate, and that protein phosphorylation regulates these determinants and segregates p...Continue Reading

Related Concepts

Point Mutation
Neurodegenerative Disorders
Aup1 protein, human
Protein Phosphorylation

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